/
/

Rett syndrome

This is part of Rare diseases.

Diagnosis: Rett syndrome

Synonyms: --

Innehåll


Date of publication: 2011-02-14
Version: 3.0

ICD 10 code

F84.3

The disease

Rett syndrome is a neurodevelopmental disorder resulting in a range of severe dysfunctions and disabilities. The syndrome occurs primarily in girls and women. Symptoms usually present at between 6 and 18 months of age. Until then, the child’s development appears to be normal.

The syndrome is named after the Viennese paediatrician Andreas Rett, who in 1965 published a study of girls and women with identical symptoms and patterns of disease progression. Although the first Swedish girls with the syndrome had been observed some years previously, Rett syndrome did not become internationally recognised until 1983 when a study was published of 35 girls from Gothenburg, Paris and Lisbon.

Occurrence

Rett syndrome is found all over the world. In Sweden, an average of six girls are born every year who will go on to develop the syndrome. If those who develop more unusual forms of the disease are included, the prevalence of the disease in Sweden is estimated at 10 per 100,000 girls and women. In total, almost 300 girls and women have been diagnosed with Rett syndrome in Sweden.

The syndrome has also been identified in a few boys and men with severe cognitive impairments. In these cases, symptoms often present earlier than they do in girls and are considerably more difficult to interpret.

Cause

The cause of the syndrome is mutations in a gene which controls the production of (codes for) a specific protein essential to the formation and function of the brain. The MECP2 gene is located on the far end of the long arm of the X chromosome (Xq28). This gene codes for the methyl CpG binding protein (MECP2), whose function is to regulate a number of other genes important for the development and functioning of nerve cells. Gene MECP2 can both activate and de-activate a number of other genes. Currently, more than 300 different mutations in gene MECP2 can be linked to Rett syndrome.

As a result of the mutation the protein does not stabilise normally, which in turn affects nerve development. Filaments in the nerve cells (axons and dendrites) do not grow and branch normally, the connections between nerve cells (synapses) become sparse, and the nerve cells become more tightly packed than normal. As the nerve cells in the brain stem are affected at an early stage, the development and maturity of the whole brain slows down. This results in impaired brain functionality as the child continues to develop. This is thought to explain how different symptoms occur at different ages. The effects on the brain stem cause lack of control of the autonomic nervous system (that part of the nervous system not subject to voluntary control). This interferes with the normal functioning of the respiratory process, the heart rate, blood pressure and circulation, and the motility of the gastrointestinal tract.

Rett syndrome is a clinical diagnosis defined on the basis of specific symptoms and the characteristic course of the disease. Over 85 per cent of the girls and women with the most common variety of Rett syndrome can be shown to have a mutation in gene MECP2. A few boys with severe cognitive disabilities, as well as girls with non-characteristic sets of symptoms, also have mutations in gene MECP2.

A mutation in the form of a duplication of gene MECP2 has also been discovered. This causes MECP2 duplication syndrome, which occurs primarily in boys. Currently it is not known why abnormally high and abnormally low levels of protein MECP2 result in equally severe symptoms.

Heredity

With few exceptions, Rett syndrome is caused by a new mutation. This means that the genetic mutation occurs in an individual for the first time and is not inherited from either parent. Consequently, parents with a child with a new mutation generally do not have an increased risk of having another child with the disorder. The risk of having more children with the syndrome is extremely small (less than 1 per cent).

Symptoms

Children with Rett syndrome often appear to develop normally until between 6 and 18 months of age. It is characteristic of the syndrome that its progression follows a set pattern, when different symptoms become more or less pronounced. Once fully developed, the syndrome is marked by severe multiple disabilities including loss of motor and communication skills, epileptic and non-epileptic seizures, dyspraxia (inability to control one’s movements) and loss of control and coordination of respiration, blood pressure and pulse. Degrees of disability vary greatly between individuals with Rett syndrome. The syndrome can be divided into four different stages.

Stage 1 (stagnation)

The first, almost imperceptible, indications of the syndrome manifest between the ages of 6 and 18 months, when general development slows down. In some children head growth, which is normal at birth, slows gradually during this period. This phase of the disease usually lasts for a few months, but can sometimes be very rapid.

Stage II (regression)

Symptoms become more severe between the ages of one and four. Children lose skills they have developed, such as fine motor skills and the ability to perform purposeful hand movements. They also cease to play, prattle or use words they have learned. It may become difficult to make contact with them and they begin to react strongly to changes in physical position and new environments. Repetitive, characteristic tongue and hand movements begin (stereotypical movements) as does pronounced tooth grinding (bruxism) of the back teeth. During this stage, which may last for weeks or months, children with Rett syndrome will have periods when they appear panic-stricken and are difficult to calm. It can be very difficult to comfort them and normal sleeping patterns are disrupted.

Stage III (plateau)

This stage is characterised by an increased interest in surroundings and a return of the will and ability to communicate. Children try to regain lost functionality and to use their remaining capacities, such as saying a few words and making purposeful hand movements. They may stand and learn to walk, but balance is usually impaired. Muscle contraction increases and many individuals develop severe curvature of the spine (scoliosis). Communicative abilities may improve and characteristic, intensive eye contact becomes more pronounced. The best conditions for the child to learn are created by making adjustments to the surroundings, and using the right methodology. For many with Rett syndrome, the plateau stage of the disease may last for decades or be life-long. Girls usually reach puberty at the usual time.

Stage IV (reduced motor skills)

This stage includes the situation of all those with Rett syndrome who cannot stand or walk. Some individuals never learn to bear their own weight, while others who have learned to stand and walk lose the skills. People with Rett syndrome often live to be middle-aged, some into their 60s and beyond. Some with the syndrome pass directly from stage II to IV.

The autonomic nervous system

Certain physical functions including the regulation of heart rate, blood pressure, peripheral blood circulation, respiration and digestion are governed by the autonomic nervous system. In Rett syndrome there are varying degrees of dysfunction in the brainstem’s control of the central autonomic nervous system.

Abnormal breathing patterns affecting pulmonary and cardiovascular function are characteristic of Rett syndrome. They can be divided into three categories: forceful breathing, abnormally shallow breathing and apneustic breathing (a series of slow deep inspirations). Valsalva breathing (attempting to forcibly exhale while the epiglottis is closed) is a common, complication to the breathing abnormalities characteristic of Retts syndrome, and affects the autonomic nerve system and brain stem functions. The consequences for the individual of Valsalva breathing depend on the category of breathing abnormality he or she manifests.

It is important to be aware that circulatory instability triggers sensations of dizziness, anxiety and panic. Impaired balance of central autonomic control may also result in cold, bluish, clammy feet.

The motility of the gastrointestinal tract (peristalsis) shifts the food along the tract and is controlled and coordinated by the autonomic nervous system. It is common that these movements are impaired and that the passage of food through the tract is unusually slow, leading to a number of symptoms of varying degrees of severity. The girls have problems swallowing and may swallow air resulting in an extended, painful stomach, and vomiting. Painful inflammation in the lower oesophagus (oesophagitis) can occur from an early age if the lower oesophageal sphincter leaks. Severe constipation is very common.

Nutrition

Many children with Rett syndrome find it difficult to take in enough calories, especially during pre-school and early school years. This can be caused by problems in coordinating movements of the mouth and throat, muscle spasms and involuntary movements, the expenditure of large amounts of energy when breathing and the inability of the intestine to absorb nutrients. It can be difficult to co-ordinate breathing and swallowing. Periods of breath holding, abnormally shallow breathing and forceful breathing can make it difficult for those with Rett syndrome to eat or swallow, although most girls greatly enjoy eating.

Growth

After normal growth during the first months of life, the child’s rate of growth generally decreases gradually and the expected growth spurt at around the age of six years is less pronounced than normal. Most adults with Rett syndrome are short, with small hands and feet. Levels of growth hormone are normal.

Deformities

Increased muscular tension, which may be different on the right and left sides of the body, can cause deformities of the back, hips, ankles and toes. Spinal deformities (scoliosis) and a hump in the upper area of the spine (kyphosis) are common. Deterioration may be rapid, especially during growth spurts. Problems become more noticeable in the teens. Often there is a gradual deterioration in adulthood as deformities do not stabilise when the child stops growing. Scoliosis and kyphosis make it difficult to balance, interfering with eye contact and communication with others. Feeding problems are also exacerbated by these deformities.

Differences in muscle tension in different parts of the body and difficulties in balancing also affect the pelvis. From an early age, increased weight bearing on one of the sitting bones can cause the body to lean to one side. This should be corrected in order to prevent scoliosis.

Bone fracture is a problem associated with Rett syndrome.

Epileptic and non-epileptic seizures

More than three-quarters of those affected have some form of seizures. The type varies greatly and epileptic and non-epileptic seizures can occur separately or together.

Epileptic seizures may start in the neonatal period or present first in the teen years, and they vary in severity. Parents are often most troubled by difficult-to-treat episodes occurring while the child is of pre-school or school age. For many individuals, epilepsy tends to become less severe with age, and some people may become symptom-free, even without medication, by early middle age.

Non-epileptic episodes with vacant spells (including attacks of agitation or panic) are common. These attacks can be difficult to distinguish from epilepsy and should not be treated with anti-epilepsy medication but be thoroughly investigated, the cause of the attacks determining their treatment.

Insomnia, agitation and irritability

Children with the syndrome often have a disturbed diurnal rhythm, which can be a problem for the whole family. Sleep studies have shown that normal sleeping patterns are broken, indicating the presence of abnormal levels of neurotransmitters in the brain. Some individuals are awake for periods during the night, when they scream or laugh loudly. Others are anxious or fearful when they wake up and breathe forcefully before they can relax again. This anxiety may be caused by inadequate respiration and should be investigated. Agitation is a common result of irregularities in autonomic control.

Oral motor function, teeth and abnormal bites

Oral motor function is often impaired, although there are wide individual variations. Both children and adults with the syndrome may have problems moving food to the backs of their mouths, and with chewing and swallowing. Food may often go down the wrong way (aspiration). Tension in jaw muscles can lead to grinding of the back teeth. This gives a characteristic grinding sound and causes severe wear on the teeth. Many people with the syndrome make involuntary tongue movements. An overbite or open bite may affect the front teeth, and the palate may be high and narrow.

Urinary tract

Recurrent urinary infections may be a consequence of the bladder not being completely emptied. Adults with the syndrome may have occasional difficulty emptying their bladders.

Development and communication

People with Rett syndrome lose conscious control of their movements, especially of their hands, at an early stage. Other neurological impairments leading to loss of function develop with age. Many have severe intellectual impairments, but cognitive and communicative abilities can sometimes be masked by motor problems, the inability to attract attention and difficulty coordinating movements.

Those with Rett syndrome understand much more, and take in more impressions and experiences, than they can express. Many are very interested in social contact. Most people with the syndrome cannot speak but often have a distinctive and intense gaze and a particular kind of direct eye contact at close distances. It is important to be aware of this form of contact, and to use for communication purposes. Nevertheless, communication can be slow and reaction times lengthy.

Diagnosis

A diagnosis of Rett syndrome is based on the clinical presentation of specific symptoms and a number of characteristic developmental abnormalities. There are internationally accepted diagnostic criteria for a diagnosis of Rett syndrome.

The discovery of the connection between the syndrome and mutations in gene MECP2 has led to great progress in confirmatory diagnosis and a better understanding of the syndrome’s biological cause. It is sometimes not possible to identify a mutation, even when girls have the appropriate combination of symptoms and the condition develops in a way characteristic of the syndrome.

If the mutation is known in the family, pre-natal diagnosis is possible.

Treatment/interventions

There are currently no treatments or preventive measures which can cure the condition or stop its development. Instead, efforts are focused on treating and alleviating symptoms, preventing and attempting to compensate for loss of functions, as well as creating the most stimulating environment and the best quality of life possible. Research shows that it is possible for those with Rett syndrome to develop with the help of special training and teaching. It is therefore important to make the most of the individual’s abilities and potential.

Treatment must always be individually structured and based on the person’s specific problems and requirements. People with Rett syndrome should be offered help to make the most of their remaining abilities and be encouraged to develop them. They require habilitation, which is planned and carried out in collaboration with specialists within paediatric neurology/neurology. A habilitation team includes professionals with special expertise in how disability affects everyday life, health and development. Support and treatment take place within the medical, educational, psychological, social and technical fields.

Gastrointestinal and feeding problems

Speech therapists and occupational therapists can give advice and support on feeding techniques, how to choose appropriate cutlery, and the seating positions which facilitate swallowing. Contact with a dietician is necessary to help in determining nutritional energy content and to provide advice on dietary supplements. Substances which change the consistency of food can be tried. The need for fluids and calories may be greater in those individuals with breathing abnormalities, including forceful breathing. It is also important that feeding is not rushed as breathing and swallowing problems are common.

Sometimes a direct connection between the abdominal wall and the stomach, a PEG (percutaneous endoscopic gastrostomy) is necessary to facilitate feeding. To stimulate the sense of taste, smaller portions should always be given by mouth. Painful ulcers may develop in the lower part of the oesophagus and require medication, which may be life-long. So that the cardia (the part of the stomach attached to the oesophagus) can close fully, an operation (Nissen fundoplication) may sometimes be required.

Constipation can be avoided by preventive measures including drinking lots of fluids, regulating the consumption of fibre, encouraging regular bowel movements and providing a relaxed and calm environment. Medication is often required to encourage movement in the gastrointestinal tract. The attending doctor or a uro/enterotherapist can give further advice.

Preventing deformities

Children who have severe motor problems and weak musculature should be examined before they reach school age and should then be followed up so that deformities of the spine can be detected. During growth spurts the child’s condition can deteriorate rapidly. A seating position which offers stability and support is important in preventing deformities, as a good sitting position makes balancing the body easier. Daily practice in standing with support is good for the skeleton, lung function, the gastrointestinal tract and for preventing contractures (loss of joint motion due to changes in non-bony tissue, including muscles.) In order to prevent fractures, muscles and tendons should be exercised and stretched, and the skeleton strengthened through exercise. A complete diet including calcium and vitamins is important. The best treatment for cold feet is physical activity such as standing and walking.

Exercises which increase mobility and strength can improve physical balance and symmetry as well as preventing deformities. Such exercises include massage, hydrotherapy, riding, music or tactile stimulation. As people with Rett syndrome cannot usually talk or grip objects, having the opportunity to move is especially important as it enables them to express their own wishes and needs.

An orthopaedic brace gives the body support and can be a means of postponing a surgical intervention, giving the child additional time to grow.

Deformities of the feet should be examined by an orthopaedic surgeon in consultation with a neurologist with experience of Rett syndrome. Treatment may include corrective surgery which alters the position of or extends tendons, or an intramuscular injection of botulism toxins.

It is vital for those who cannot walk that they are provided with chairs and wheelchairs which provide back support and encourage a good seating position. The ability to stand can be retained if individuals use a standing frame for example. It should also be possible for them to change position and stretch to their full height. Adjustments to accommodation, and other places where the individual with the syndrome spends time, may be necessary.

Respiratory and cardiovascular function

It is important to discover whether the child has a breathing abnormality, and if so, how it affects cardiovascular function. Certain types of respiratory abnormalities can be treated with medication, while others may require breathing aids.

Epileptic and non-epileptic seizures

Epilepsy is treated with medication determined by the type of seizure, but it can be difficult to prevent attacks completely. As the child is growing up, a paediatric neurologist should monitor the child so medication can be adjusted. Sometimes medication can be successively reduced in adulthood, and stopped entirely in middle age. A person with Rett syndrome should be monitored by a neurologist.

Dental care

Tooth brushing and dental treatment can be problematical for the individual, so supplementary preventive care is necessary. A pedodontist (a dentist specialising in children) should be consulted at an early stage to make a dental examination and plan treatment. When necessary, tooth-grinding should be followed up and a dental bite guard provided.

Jaw and neck muscles may be tense and painful and specialist massage can assist relaxation.

Insomnia, agitation and irritability

Melatonin treatment has been tried, with varying results. Sometimes breathing aids may be needed at night. As those with abnormally shallow breathing can be extra sensitive to morphine and morphine derivatives, such medication should not be administered to them. Diazepam should be used only with the greatest care.

It is important to avoid stimuli which might cause agitation and over-excitement, and find instead calming activities such as music. Risperidone may sometimes be used in cases of severe anxiety. Prior to treatment, the individual’s type of breathing abnormality should be identified.

Development and communication

People with Rett syndrome must be able to develop their motor and communication skills according to their individual capacities. As they find it difficult to take initiatives or make purposeful movements (apraxia/dyspraxia) there is a long delay before they respond. For this reason, motivation should be actively encouraged and stimulated. Most people with the syndrome enjoy listening to music or stories and carrying out manageable tasks.

An investigation into how the individual communicates is important. This provides the basis for determining which form of alternative and complementary communication (ACC) to use. These girls generally retain control over their eye movements. Eye function usually remains good and serious changes to, or impairment of, vision are unusual. The ability to control eye movements and indicate direction can be used to communicate. With the help of a touch screen, special switches and eye pointing it is possible to communicate through pictures on a computer screen.

Girls with Rett syndrome require specialist teaching methodology.

Habilitation

Habilitation may include assessments, treatment, assistance with choice of aids, information about disabilities and counselling. It may also include information about support offered by the local authority as well as advice on the way accommodation and other environments can be adapted to the child’s needs. Parents and siblings may also receive support. There should be close contact with the local authority, which can offer different kinds of help including personal assistance, a contact family or short-term accommodation, to make daily life easier.

Adults with Rett syndrome require continued individual habilitation and support in their daily lives. This may take the form of support and care in accommodation offering specialist services and daily activities. Personal assistance enables individuals with Rett syndrome to participate in activities and improves their quality of life. Adults require continued contact with habilitation and general medical services, as well as with certain specialists including an orthopaedic surgeon.

Practical advice

--

National and regional resources in Sweden

The Rett Center is a national center of expertise offering clinical diagnostics and medical treatment, as well as being involved in research and the spread of information. The Rett Center, Frösö Strand, Box 601, SE-832 23 Frösön, Sweden.Tel: +46 63 15 48 10, fax: +46 63 15 45 00, email: rettcenter@jll.se, www.rettcenter.se. Contact senior consultant Ingegerd Witt Engerström. Tel: +46 705 56 52 57, email: ingegerd.witt.engerstrom@jll.se.

A multi-disciplinary team with expertise in neuropaediatrics and respiratory physiology is located at Astrid Lindgren Children’s Hospital and the Karolinska Institute, Sweden. Contact Maud Eriksson. Tel: +46 8 585 800 00.

A neuropaediatric and neuropsychiatric team specialising in children and young people with rare disabilities, including Rett syndrome, is located at The Queen Silvia Children’s Hospital in Gothenburg, Sweden. There are also specialist teams for Rett-related gastrointestinal problems and epilepsy. Contact: Senior physician Barbro Westerberg (gastrointestinal examinations), The Queen Silvia Children’s Hospital, tel: +46 31 343 40 00, and Senior physician Ragny Kristjánsdóttir (epilepsy), Children’s and Young People’s Habilitation, tel: +46 31 734 35 00.

At “Ovanliga Diagnoser, Handikapp & Habilitering”, Stockholm County Council, there is a multi-disciplinary team for Rett syndrome, www.habilitering.nu/ovanligadiagnoser
Contact Kristina Gustafsson-Bonnier. Tel: +46 8 690 60 33, email: kristina.gustafsson-bonnier@sll.se.

Expertise in Rett-related orofacial problems can be found at Mun-H-Center, Institute of Odontology, Medicinaregatan 12 A, SE-413 90 Gothenburg, Sweden. Tel: +46 31 750 92 00, fax: +46 31 750 92 01, email mun-h-center@vgregion.se, www.mun-h-center.se

Resource personnel

Senior physician Maud Eriksson and physician Rickard Nergård, Astrid Lindgren Children’s Hospital in Huddinge, SE-141 86 Stockholm, Sweden. Tel: +46 8 585 800 00. Also Senior associate physician Margareta Albåge, Associate professor Miriam Katz-Salamon and physician Malin Rohdin, Astrid Lindgren Children’s Hospital in Solna, SE-171 76 Stockholm, Sweden. Tel: +46 8 517 700 00.

Professor Christopher Gillberg, Gothenburg University, Gothenburg Unit For Child and Adolescent Psychiatry, Kungsgatan 12, SE-411 19 Gothenburg, Sweden. Email: christopher.gillberg@pediat.gu.se.

Senior dental surgeon Karin Högkil, Eastmaninstitutet, Dalagatan 11, SE-113 24 Stockholm, Sweden. Tel: +46 8 123 165 38.

Senior physician Ragny Kristjánsdóttir, Habilitation and Health, (Children and Young People), Näverlursgatan 38, SE-421 42 Västra Frölunda, Sweden. Tel: +46 31 734 35 00.

Senior physician Barbro Westerberg, The Queen Silvia Children’s Hospital, SE-416 85 Gothenburg, Sweden. Tel: +46 31 343 40 00.

Senior consultant Ingegerd Witt Engerström and colleagues at Rett Center, Frösö Strand, Box 601, SE-832 23 Frösön, Sweden. Tel: +46 63 15 48 10. The team includes neuropaediatrician Dr Ingegerd Witt Engerström (email: ingegerd.witt.engerstrom@jll.se, tel: +46 705 56 52 57), specialist in autonomic neurophysiology Dr Peter Julu, speech therapist Helena Wandin, music therapist Märith Bergström-Isacsson, psychologist Martina Holmbom, occupational therapist Åsa-Sara Sernheim and physiotherapist Lena Svedberg. In addition, specialist in paediatric orthopaedics Dr Lars Rehnberg, pedodontist Kristina Palm, senior physicist Stig Hansen and senior EEG technician Flora Apartopoulos also participate in the work of the Center. For more information see www.rettcenter.se.

Courses, exchanges of experience, recreation

Family conferences and camps are organised by the association, Rett Syndrome in Sweden (RSIS). For further information contact RSIS. (Find address under, “Organizations for the disabled/patient associations etc.”)

Ågrenska is a national competence centre for rare diseases and its families’ programme arranges stays for children and young people with rare diseases and their families. Ågrenska is open to families from the whole of Sweden and focuses particularly on the needs of children and young people with rare diseases. Every year some adults with rare diseases also visit Ågrenska. Information is available from Ågrenska, Box 2058, SE-436 02 Hovås, Sweden. Tel: +46 31 750 91 00, fax: +46 31 91 19 79, email: agrenska@agrenska.se, www.agrenska.se.

Organizations for the disabled/patient associations

The association, Rett Syndrome in Sweden (RSIS), email: info@rsis.se, www.rsis.se. The Chair is Lars Bergkvist, email: lars.bergkvist@rsis.se.

Rare Diseases Sweden, Box 1386, SE-172 27 Sundbyberg, Sweden. Tel: +46 8 764 49 99, fax: +46 8 546 404 94, email: info@sallsyntadiagnoser.se, www.sallsyntadiagnoser.se.
Rare Diseases Sweden is a national association representing people with rare diseases and varying disabilities.

There is an international association, International Rett Syndrome Foundation (IRSF), www.rettsyndrome.org. There is also a European association, Rett Syndrome Europe (RSE), www.rettsyndrome.eu, and a European working group, EWGRS (European working group on Rett syndrome), www.rettmeeting.org.

Courses, exchanges of experience for personnel

Courses, workshops, conferences and seminars for multi-disciplinary teams or specialist groups within habilitation, healthcare and schools, are organised by the Rett Center. For further information contact Rett Center. (Find address under, “National and regional resources in Sweden.”)

Courses for personal assistants are organised by the association, Rett Syndrome in Sweden (RSIS) in collaboration with the Rett Center. For further information contact RSIS or the Rett Center.(Find address under, “Organizations for the disabled/patient associations etc.”)

Research and development (R&D)

Clinical research in several areas is ongoing at the Rett Center. Research includes the functions of the brain stem and central autonomic control in Rett syndrome, gross motor skills and autonomic control, as well as the role of music in the brain stem’s regulatory effect on the autonomic nerve system. There has been long-term clinical monitoring of people with Rett syndrome for the last 25 years.

Research within respiratory physiology is being carried out at the Astrid Lindgren Children’s Hospital in Solna/Huddinge and the Karolinska Institute, Sweden. For contacts, see under “Resource personnel.”

Genetic research is under way in Gothenburg. Contact Professor Bengt Hagberg and Associate professor Mårten Kyllerman, The Queen Silvia Children’s Hospital. Also, associate clinical geneticist Anna Erlandson and doctoral candidate Saideh Rajaei, Clinical genetics.

Information material

An information leaflet on Rett syndrome that summarises the information in this database text is available free of charge from the customer service department of the Swedish National Board of Health and Welfare (in Swedish only, article number 2010-5-21.) Address: SE-120 88 Stockholm, Sweden. Tel: +46 75 247 38 80, fax: +46 35 19 75 29, email: publikationsservice@socialstyrelsen.se. Postage will be charged for bulk orders.

Julu PO, Witt Engerström I, Hansen S et al. Cardiorespiratory challenges in Rett’s syndrome. Lancet. 2008 June 14:371(9629):1981–3. A longer version, Addressing the cardiorespiratory challenges posed by Rett Syndrome in medicine: The Frösö declaration. Can be downloaded at www.rettcenter.se and can also be ordered from the Rett Center. Find address under, “National and regional resources in Sweden.”

Rett syndrome – What are the signs and what can be done? Explanations of treatment, and recommendations from the treatment team at the Rett Center (2005). ( In Swedish only.) Can be downloaded at www.rettcenter.se and can also be ordered from the Rett Center. Find address under “National and regional resources in Sweden.”

Information folders (in Swedish and English) on Rett syndrome, brain stem examinations, music therapy, the Rett Center and Accomodation at the Rett Center. Can be downloaded at www.rettcenter.se and can also be ordered from the Rett Center. Find address under “National and regional resources in Sweden.”

På Rett väg (in Swedish only) Information leaflet issued twice a year. Can be downloaded at www.rettcenter.se and can also be ordered from the Rett Center. Find address under “National and regional resources in Sweden.”

A pocket-size information folder (in Swedish only) can be ordered from RSIS, email info@rsis.nu.

Newsletter from Ågrenska, nr 263 (2006). (In Swedish only).Can be ordered from Ågrenska, Box 2058, SE-436 02 Hovås, Sweden. Tel: +46 31 750 91 00, fax: +46 31 91 19 79, email: agrenska@agrenska.se. Newsletter also available at www.agrenska.se.

Rett syndrome. Information folder (in Norwegian only) from, Senter for sjeldne funksjonshemningar, Frambu and the Norwegian Association for Rett Syndrome (2005). Order from, Senter for sjeldne funksjonshemninger, Informasjonsseksjonen, NO-1404 Siggerud, Norway.Tel: +47 64 85 60 00, email info@frambu.no.

Films

The Musement. A rhythmic movement class for children with Rett syndrome or any children who like to move to music run by Märith Bergström-Isacsson, music therapist and Gunilla Larsson, physiotherapist, Rett Center, Frösön, Sweden 2008. May be ordered from the Rett Center. Find address under “National and regional resources in Sweden.” (There is also a Swedish version, Musorik.)

(Jag talar med ögonen.) I speak with my eyes - Retts syndrome. The film can be ordered from RSIS, email info@rsis.nu.

Understanding Rett Disorder – A Guide for Professionals, Alison Kerr 2006. Can be ordered from the Rett Center. Find address under “National and regional resources in Sweden.”

The Rett syndrome handbook with CD (2007). Can be ordered from the International Rett Syndrome Foundation (IRSF), www.rettsyndrome.org.

Literature

Amir RE, Van den Veyver IB, Wan M, Tran CQ, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in x-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet 1999; 23: 185-188.

Armstrong DD, Kinney HC. The neuropathology of the Rett disorder. Rett disorder and the developing brain. Oxford University Press 2005.

Bergstrom-Isacsson M, Julu POO, Witt-Engerstrom I. Autonomic responses to music and vibroacoustic therapy in Rett syndrome: A controlled within-subject study. Nordic Journal of Music Therapy 2007; 16.

Cass H, Reilly S, Owen L, Wisbeach A, Weekes L, Slonims V et al. Findings from a multidisciplinary clinical case series of females with Rett syndrome. Dev Med Child Neurol 2003; 45: 325-337.

Downs J, Bergman A, Carter P, Anderson A, Palmer G, Roye D et al. Guidelines for management of scoliosis in Rett syndrome patients based on expert consensus and clinical evidence. Spine 2009; 34: 606-617.

Diagnostic Criteria Working Group. Diagnostic criteria for Rett syndrome. Ann Neurol 1988; 23: 425-428.

Einspieler C, Kerr AM, Prechtl HFR. Abnormal general movements in girls with Rett disorder: The first four months of life. Brain Dev 2005; 27: 1-6.

Erlandson A, Hagberg B. MECP2 abnormality phenotypes: clinicopathologic area with broad variability. J Child Neurol 2005; 20: 727-732.

Hagberg B. Rett syndrome: long-term clinical follow-up experiences over four decades. J Child Neurol 2005; 20: 722-727.

Hagberg B. Clinical manifestations and stages of Rett syndrome. Ment Retard Dev Disabil Res Rev 2002; 8: 61-65.

Hagberg B, Hanefeld F, Percy A, Skjeldal O. An update on clinically applicable diagnostic criteria in Rett syndrome. Eur J Pediatr Neurol 2002; 6: 293-297.

Hagberg B. Rett Syndrome: clinical peculiarities and biological mysteries. Acta Paediatr 1995; 6: 971-976.

Hoffbuhr K, Devaney JM, LaFleur B, Sirianni MS, Scacheri C, Giron J. MeCP2 mutations in children with and without the phenotype of Rett syndrome. Neurology 2001; 56: 1486-1495.

Huppke P, Held M, Laccone F, Hanefeld F. The spectrum of phenotypes in females with Rett syndrome. Brain Dev 2003; 25: 346-351.

Julu PO, Kerr AM, Apartopoulus F, Al-Rawas S, Witt Engerström I, Engerström L. Characterisation of breathing and associated central autonomic dysfunction in the Rett disorder. Arch Dis Child 2001; 85: 29-37.

Julu PO, Witt Engerström I. Assessment of the maturity related brainstem functions reveals the heterogeneous phenotypes and facilitates clinical management of Rett syndrome. Brain Dev 2005; 27: 43-53.

Julu PO, Witt Engerström I, Hansen S, Apartopoulos F, Enger¬ström B, Pini G et al. Cardiorespiratory challenges in Rett’s syndrome. The Lancet 2008; 371: 1981-1983.

Kerr AM, Webb P, Prescott RJ, Milne Y. Results of surgery for scoliosis in Rett syndrome. J Child Neurol 2003; 18: 703-708.

Larsson G, Witt Engerström I. Gross motor ability in Rett syndrome – the power of expectation, motivation and planning. Brain Dev 2001; 23: 77-81.

Larsson G, Lindström B, Witt Engerström I. Rett syndrome from a family perspective; The Swedish Rett Center survey. Brain Dev 2005; 27: 14-19.

Lavås J, Slotte A, Jochym-Nygren M, van Doorn J, Witt Engerström I. Communication and eating proficiency in 125 females with Rett syndrome -The Swedish Rett Center Survey. Disabil Rehabil 2006; 28: 1267-1279.

Leonard H, Silberstein J, Falk R, Houwink-Manville I, Ellaway C, Raffaele LS. Occurrence of Rett syndrome in males. J Child Neurol 2001; 16: 333-338.

Lindberg B. Understanding Rett syndrome – A practical guide for parents, teachers and therapists. Second revised edition, Hogrefe 2006.

Moog U, Smeets EE, van Roozendaal KE, Schoenmakers S, Herbergs J, Schoonbrood-Lenssen AM et al. Neurodevelopmental disorders in males related to the gene causing Rett syndrome in females (MECP2). Eur J Paediatr Neurol 2003; 7: 5-12.

Nomura Y. Early behavior characteristics and sleep disturbances in Rett syndrome. Brain Dev 2005; 27: 35-42.

Nomura Y, Kerr A, Witt Engerström I. Rett syndrome; early behavior and possibilities for intervention. Brain Dev Supplement 1, 2005.

Nuber U, Kriaucionis S, Roloff T, Guy J, Selfridge J, Steinhoff C et al. Up-regulation of glucocorticoid-regulated genes in a mouse model of Rett syndrome. Hum Mol Gen 2005; 14: 2247-2256.

Percy, A.K. Rett syndrome: recent research progress. J Child Neurol 2008; 23: 543-549.

Qvarfordt I, Witt Engerström I, Eliasson A-C. Guided eating or passive feeding – Three girls with Rett syndrome. Scand J Occupational Therapy 2008; 7: 1-7.

Rohdin M, Fernell E, Eriksson M, Albåge M, Lagercrantz H, Katz-Salamon M. Disturbances in cardiorespiratory function during day and night in Rett syndrome. Pediatr Neurol 2007; 37: 338-344.

Schanen C, Houwink EJ, Dorrani N, Lane J, Everett R, Feng A et al. Phenotypic manifestations of MECP2 mutations in classical and atypical Rett syndrome. Am J Med Genet A 2004; 126: 129-140.

Smeets E, Terhal P, Casaer P, Peters A, Midro A, Schollen E et al. Rett syndrome in females with CTS hot spot deletions. A disorder profile. Am J Med Genet A 2005; 132: 117-120.

Witt Engerström I. Rett Syndrome in Sweden. Neurodevelopment - disability - pathophysiology. Acta Paediatr Scand 1990; Suppl 369 (dissertation).

Witt Engerström I. Age related occurrence of signs and symptoms in Rett syndrome. Brain Dev 1992; 14 : 11-20.

Witt Engerström I, Larsson G, Bergström-Isacsson M, Wesslund B, Quarfordt I, Jochym-Nygren M. Rett syndrom – Hur kan det se ut och vad kan man göra? Östersund 2005.

Ylisaukko-Oja T, Rehnström K, Vanhala R, Kempas E, von Koskull H, Tengström C et al. MECP2 mutation analysis in patients with mental retardation. Am J Med Genet A 2005; 132: 121-124.

Books

Kerr A, Witt Engerström I. Rett disorder and the developing brain. Oxford University Press, 2001 and 2005.

Database references

OMIM (Online Mendelian Inheritance in Man)
www.ncbi.nlm.nih.gov/omim 
Search: rett syndrome

GeneReviews (University of Washington),
www.genetests.org (select GeneReviews, then Titles)
Search: rett syndrome

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical experts who wrote the draft of this information material are Professor Emeritus Bengt Hagberg, The Queen Silvia Children’s Hospital in Gothenburg, and Senior physician Ingegerd Witt Engerström, Rett Center, Frösö Strand.

The revisions have been made by Senior consultant Ingegerd Witt Engerström, Rett Center, Frösö Strand, Senior physician Maud Eriksson, Astrid Lindgren Children’s Hospital, Stockholm, and Barbro Westerberg, The Queen Silvia Children’s Hospital, Gothenburg, Sweden.

The relevant organisations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

An expert group on rare diseases, affiliated with the University of Gothenburg , approved the material prior to publication.

Date of publication: 2011-02-14
Version: 3.0
Publication date of the Swedish version: 2010-09-14

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 400, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.

 

About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.